study of haplo-hsct + rivogenlecleucel vs haplo-hsct + post transplant cyclophosphamide in patients with aml or mds

Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes

Summary: this study compares the safety and effectiveness of giving rivogenlecleucel (bpx-501 t cells) to patients with aml or mds post haploidentical hematopoietic stem cell transplant compared to post-transplant cyclophosphamide.

in the phase 2 portion, participants will undergo αβ t cell and cd19+ b cell depleted haploidentical hsct followed by an infusion of a fixed dose of rivogenlecleucel (bpx-501 t cells) per kg. these participants will be evaluated for prespecified dose limiting toxicities (dlts) for a 100-day dose limiting toxicity window. following completion of the phase 2 portion, participants will be enrolled and randomized to one of two treatment arms in the phase 3 portion. * arm a:αβ t-cell and cd19+ b-cell-depleted haplo-hsct plus treatment with rivogenlecleucel * arm b: haplo-hsct plus post transplant cyclophosphamide pediatric patients ages 12-17 will also be included in us only.

Eligibility criteria:
inclusion criteria: signed informed consent meeting institutional criteria to undergo allogenic hsct age 18-70 y/o (12-70 y/o in us only) patients with aml or mds as defined below: aml patients patients with intermediate to adverse aml as defined by eln (dohner, 2017). * aml in first complete remission (cr1) with high-risk features defined as \> 1 cycle of induction therapy required to achieve remission or preceding mds or myeloproliferative disease * aml in cr1 with intermediate-risk features * aml in second or subsequent complete response * aml with myelodysplasia-related changes (aml-mrc) * therapy related aml in first or subsequent complete remission * de novo aml in second or subsequent complete remission mds patients * high or very-high risk mds by ipss-r classification * intermediate risk or higher mds patients who failed a hypomethylating agent lack of suitable conventional donor (i.e. hla 10/10 related or unrelated donor) at least a 5/10 genotypic identical haplotype match the donor and recipient must be identical, at least one allele of each of the following genetic loci: hla-a, hla-b, hla-c, hla-drb1, and hla-dqb1 patients with adequate organ function eastern cooperative oncology group (ecog) performance status: 0-2 exclusion criteria: * hla 10/10 allele matched (hla-a,-b,-c,-drbl, and dqb1) related donor or unrelated donor * autologous hematopoietic stem cell transplant ≤ 3 months before enrollment * prior allogeneic transplantation * active cns involvement by malignant cells (less than 2 months from the conditioning) * current uncontrolled clinically active bacterial, viral or fungal infection * positive hiv serology or viral rna * pregnancy (positive serum or urine βhcg test) or breast-feeding * fertile men or women unwilling to use effective forms of birth control or abstinence for a year after transplantation * radiographic, histologic, or known history of cirrhosis * overlapping mds and myeloproliferative neoplasms (mpn) disease * patients with acute promyelocytic leukemia (apl) * known hypersensitivity to dimethyl sulfoxide (dmso)